2. Academic Validation
  3. Discovery of chalcone-modified estradiol analogs as antitumour agents that Inhibit tumour angiogenesis and epithelial to mesenchymal transition

Discovery of chalcone-modified estradiol analogs as antitumour agents that Inhibit tumour angiogenesis and epithelial to mesenchymal transition

  • Eur J Med Chem. 2019 Aug 15:176:135-148. doi: 10.1016/j.ejmech.2019.04.071.
Cong Wang 1,  Leilei Li 1,  Dongyang Fu 1,  Tiantian Qin 1,  Yange Ran 1,  Feng Xu 1,  Xinrui Du 2,  Haiying Gao 3,  Shuaijun Sun 4,  Tengjiao Yang 5,  Xueyan Zhang 1,  Junfeng Huo 1,  Wen Zhao 1,  Zhenzhong Zhang 1,  Xiufang Shi 6
Affiliations

Affiliations

  • 1 Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Key Laboratory of Henan Province for Drug Quality and Evaluation, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, PR China.
  • 2 Department of Clinical Medicine, Zhengzhou University, 40 Daxue Road, Zhengzhou, Henan, 450052, China.
  • 3 Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Key Laboratory of Henan Province for Drug Quality and Evaluation, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, PR China; Department of Pharmacy, People's Hospital of Daqing, 241 Jianshe Road, Development District, Daqing, 163316, Heilongjiang, China.
  • 4 Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Key Laboratory of Henan Province for Drug Quality and Evaluation, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, PR China; Department of Pharmacy, Zhengzhou Central Hospital Affiliated to Zhengzhou University, 195 Tongbai Road, Zhengzhou, 450053, Henan, China.
  • 5 HeNan No.3 Provincial People's Hospital, Funiu Road, Zhongyuan District, Zhengzhoum, 450000, Henan, China.
  • 6 Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Key Laboratory of Henan Province for Drug Quality and Evaluation, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, PR China. Electronic address: xfshi@zzu.edu.cn.
PMID: 31102934 DOI: 10.1016/j.ejmech.2019.04.071
Abstract

Angiogenesis plays an essential role in tumourigenesis and tumour progression, and anti-angiogenesis therapies have shown promising antitumour effects in solid tumours. 2-Methoxyestradiol (2ME2), an Endogenous Metabolite of estradiol, has been regarded as a potential antitumour agent mainly targeting angiogenesis. Here we synthesized a novel series of Chalcones based on 2-methoxyestradiol and evaluated their potential activities against tumours. Compound 11e was demonstrated to have potent antiangiogenic activity. Further studies showed that 11e suppressed tumour growth in human breast Cancer (MCF-7) xenograft models without obvious side effects. Evaluation of the mechanism revealed that 11e targeted the epithelial to mesenchymal transition (EMT) process in MCF-7 cells and inhibited HUVEC migration and then contributed to hindrance of angiogenesis. Thus, 11e may be a promising antitumour agent with excellent efficacy and low toxicity.

Keywords

2-Methoxyestradiol; Angiogenesis; Antitumour; EMT; Migration.

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